Pathways of glutamine and organic acid metabolism in renal cortex in chronic metabolic acidosis

Abstract

The metabolism of labeled glutamine and of several labeled organic acid anions was compared in tissue slices of renal cortex from chronically acidotic and alkalotic littermate dogs. ¹⁵NH₃ formation and ¹⁵N-amideglutamine utilization were significantly increased by slices from acidotic animals providing further evidence for the similarity of the metabolic responses seen in the tissue slice system and the physiologic effects produced by chronic metabolic acidosis on renal metabolism in the intact animal. Slices from acidotic dogs formed more ¹⁴CO₂ and glucose-¹⁴C than did slices from alkalotic animals when labeled glutamine, citrate, or malate was used as substrate but ¹⁴CO₂ production from pyruvate-1-¹⁴C was slightly reduced in acidotic tissue. With most of the substrates used glucose-¹⁴C formation was small compared with ¹⁴CO₂ formation. Using the amount of glucose-¹⁴C formed, the expected ¹⁴CO₂ production was calculated based on the hypothesis that the primary site of action of metabolic acidosis is on a cytoplasmic step in gluconeogenesis. The actual difference in ¹⁴CO₂ production between slices from acidotic and alkalotic animals always greatly exceeded this predicted amount, indicating that stimulation of gluconeogenesis represents a minor metabolic response to chronic metabolic acidosis. Evidence from experiments with citrate labeled in various positions showed that metabolic acidosis has its principal effect on an early step in substrate metabolism which must be intramitochondrial in location.